Throughout their lifetime, men are at higher risk of coronary heart disease (CHD) than women, however, after menopause this difference is attenuated. This observation suggests that endogenous sex hormones could be associated with CHD risk. There is some evidence indicating that the effect of sex hormones on CHD risk could be mediated, in part, by alterations in lipid levels or other CHD risk factors. However, other evidence supports an independent relationship of circulating hormone levels with CHD risk. For example, we recently reported a significant positive association between serum total testosterone concentration and the presence of subclinical coronary artery calcium (CAC) in young adult men that was independent of other CHD risk factors. Conversely, we showed an independent inverse association between total testosterone concentration and carotid intimal-medial wall thickness (IMT) in women. Overall, these results suggest that the influence of the hormonal milieu on subclinical atherosclerosis may not be the same in men compared to that in women. The overall objective of the proposed project is to examine the associations of serum sex hormone concentrations with the presence and progression of subclinical atherosclerosis in 3,259 male and 2,802 postmenopausal female participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Subclinical atherosclerosis will be identified using both CAC and carotid IMT. Progression will be identified by the change in CAC over 3.5 years. Circulating concentrations of total (and free) testosterone (T), dehydroepiandrosterone (DHEA), 17 beta-estradiol (E2), and sex hormone binding globulin (SHBG) in stored serum samples collected at the MESA baseline exam will be assessed. Laboratory results will be merged with existing demographic, anthropometric, lifestyle, CHD risk factor, and subclinical disease data collected in MESA. Cross-sectional and prospective methods of statistical analysis will be used to assess the proposed associations. MESA is particularly well suited for disentangling the effects of hormonal factors and CHD risk factors on subclinical atherosclerosis because of the availability of high-quality data, serum samples, and CAC and IMT measurements in a large multi-ethnic population of men and women. [unreadable] [unreadable]